Forebrain-Cerebellum Interactions in Trace Conditioning

描述（由申请人提供）：我们建议使用眼皮的痕迹条件反射来研究前额皮质调节工作记忆的神经机制。我们已经证明，兔的眼皮轨迹条件反射是一种工作记忆任务，涉及前额叶皮层所谓的“延迟细胞”的持续活动。关于延迟细胞和工作记忆机制的许多基本问题仍未得到解答，这主要是由于灵长类动物研究的局限性：传统的工作记忆研究系统。具体来说，在兔子身上使用微量条件反射使得研究PFC延迟细胞活动的起源成为可能：学习在其中扮演了什么角色？对于延迟细胞来说PFC的输入是什么？因为在完全不熟悉任务的兔子身上录音是可行的，而在灵长类动物身上是不可行的，所以这些问题变得可行，而且回答起来也负担得起。我们将使用PFC神经元的记录来确定延迟细胞活动是如何产生的，并描述当任务需求改变时控制延迟细胞反应变化的规则。兔实验也对投射到前额皮质的参与微量条件反射和延迟细胞活动的通路进行了可行的分析。因此，这些研究的完成将对工作记忆的形成机制及其受环境需求变化的调节产生根本性的新见解。这些知识将极大地促进我们制定预防或治疗一系列神经系统疾病的策略的能力，这些疾病似乎与工作记忆缺陷有关，包括注意力障碍和与年龄有关的痴呆症。

DESCRIPTION (provided by applicant): We propose to use trace eyelid conditioning to study the neural mechanisms operating in prefrontal cortex to mediate working memory. We have demonstrated that trace eyelid conditioning in rabbit is a working memory task that involves the persistent activity of the so called "delay cells" of prefrontal cortex. There are many fundamental questions about delay cells and the mechanisms of working memory that have remained unanswered largely owing to limitations of studies in primates: the traditional system for working memory studies. Specifically, working with trace conditioning in rabbits makes it feasible to study the origins of delay cell activity in PFC: what roles are played by learning? what are the inputs to PFC that are necessary for delay cells? Because recordings are feasible in rabbits completely na¿ve to the task, which is not feasible with primates, such questions become feasible and affordable to answer. We will use recordings from PFC neurons to determine how delay cell activity arises and to characterize the rules that govern changes in delay cell responding as task demands are changed. Rabbit studies also make feasible analysis of the pathways projecting to prefrontal cortex that are involved in trace conditioning and delay cell activity. The completion of these studies will therefore yield fundamental new insights into the mechanisms responsible for the formation of working memories and their modulation by changes in environmental demands. Such knowledge will greatly facilitate our ability to develop strategies for the prevention or treatment of a host of neurological disorders that appear to relate to working memory deficits, including attention disorders and age-related dementias.